Pages

Friday, June 24, 2011

PTSD, Neurogenesis, and Panic Attacks

These three articles have kind of found themselves linked in my head through my recent return to trauma studies as part of my internship work. The most interesting of the three to me is the finding that fearful experiences (i.e., trauma) causes neurogenesis in the hippocampus (a major memory hub), and those cells act as blank slates for the newly encoded memories (making them apparently much harder to eradicate, or least to remove the negative charge).

Researchers have discovered a link between neurons and fearful memories. The new study suggests that in fearful situations, new neurons, created by the hippocampus, act as a canvas on which new memories are imprinted. Researchers state that these newly generated neurons are responsible for strong memories linked to fearful and traumatic experiences. “We remember emotional events much more strongly than daily experiences, and for a long time we have known that connections between the amygdala and hippocampus help to encode this emotional information,” said Kaufer, an assistant professor of integrative biology and a member of University of California, Berkeley’s Wills Neuroscience Institute. “Our research shows that amygdala input actually pushes the hippocampus to make new neurons from a unique population of neural stem cells. This provides completely new cells that get activated in response to emotional input.”

These results are significant for exploring the symptoms related to post-traumatic stress and other issues that develop as a result of emotional memory. “Many affective disorders involve disordered emotional memories like PTSD, depression and anxiety. We think that newborn neurons may play a role in creating these emotional memories,” she said.

Kaufer conducted the study with Aaron Friedman and Elizabeth Kirby, lead author, by altering the basolateral amygdala of rats, resulting in decreased production of new cells. They elicited a fear response in the rats, and subjected them to the same fearful experience, and a non-threatening experience, the following day. They discovered that the newly created neurons were active as a result of the fearful event, but the neurons did not react in the altered basolateral amygdala.” The research suggests that newborn neurons play a role not only in the formation of memory, but also in helping to create the emotional context of memory,” Kirby said. The researchers hope to further explore the effects of similar negative emotions, such as anxiety or stress, on the amygdala to determine the impact on newly developed neurons.

Those are some important findings - it may be possible to inhibit neurogenesis in the hours following a rape, witnessing a murder, and so on, and thereby prevent or reduce the symptoms of PTSD.

The finding comes a year after brain researcher Fred Gage at the Salk Institute for Biological Studies in La Jolla, Calif., showed that the formation of new memories is associated with increased activation of two-week-old newborn nerve cells in the hippocampus that are derived from adult neural stem cells. Adult stem cells appear to differentiate continually into new nerve cells - nearly 100 each day - yet half of those newborn neurons are slated for death within four weeks after their birth. If they are highly activated, however - such as in learning new complex information - many more of them will survive and presumably help in establishing new memories in the brain.

Kaufer, who conducts research on the effects of stress on the brain, knew that many types of positive and negative experiences, such as exercise and stress, affect the rate of neurogenesis in the hippocampus. Along with graduate students Elizabeth Kirby, the lead author of the study, and Aaron Friedman, she was intrigued by the idea that emotions might affect neurogenesis in the hippocampus, since the brain's clearinghouse for emotions, the amygdala, is connected to the hippocampus via multiple neural circuits. To test this, Kirby focused on the basolateral amygdala, the region of the almond-shaped structure that handles negative emotions, including stress, anxiety and fear.

Using rats, Kirby surgically destroyed the basolateral amygdala and discovered that the production of new nerve cells in the hippocampus decreased. To make sure that the cell damage created when the amygdala was surgically destroyed was not affecting the experiment, the researchers borrowed a gene therapy technique from Robert Sapolsky's lab at Stanford University to genetically introduce potassium channels into the amygdala, which shut down the activity of the nerve cells without causing injury. This also decreased neurogenesis in the hippocampus.

They next tested Gage's theory that new neurons are especially sensitive to input two weeks after they form. Kirby and Kaufer labeled hippocampal cells created over a three-day period in a group of rats, and then conditioned a fear response in these rats two weeks later. They then confronted the rats with the same fearful situation or a neutral yet novel context the next day. When they examined the brains, they found that the newborn neurons had been specifically activated by the fearful situation. However, when they destroyed the basolateral amygdala, new neurons were no longer activated in response to the fearful memory.

"The research suggests that newborn neurons play a role not only in the formation of memory, but also in helping to create the emotional context of memory," Kirby said. It also suggests that the basolateral amygdala drives the ability of new neurons to be part of an emotional memory.

The team now plans to see whether other negative stimuli, such as stress and anxiety, similarly cooperate with amygdala activity to alter neurogenesis in the hippocampus.

* * * * * * *

This article from Psychology Today (The Mindful Self-Express blog) has been hanging around since early May, but I kept it in my tabs because it shows a connection between PTSD and other forms of disease - more confirmation of the "stress causes disease" hypothesis. Greenberg sees the whole mind-body-spirit thing as inseparable.

The trauma, pain and suffering of our nation's veterans in the recent Iraq and Afghanistan wars has been tremendous. About 20% suffer from Post-Traumatic Stress Disorder (PTSD), a devastating condition characterized by long-term nightmares, feelings of terror, problems in intimate relationships, anger, emotional numbing and suicide risk.

The DSMIV-TR, the major diagnostic manual of the American Psychiatric Association conceptualizes PTSD as an Anxiety Disorder and has research-based criteria for its for its diagnosis. Cognitive-Behavioral treatments are effective at decreasing PTSD symptoms and are considered state of the art. Yet I do not consider PTSD to be a mental health problem. Rather, I see it as a chronic, systemic problem of mind-body-spirit in which long-term stress responses deplete both mental and physical health.

I have been trained in Health Psychology and the Biopsychosocial Model (Engel, 1977) which, in contrast to our current fragmented approach to healthcare, does not see mental and physical health problems as separate. Having major depression, for example, substantially elevates the risk of developing chronic pain and heart disease. Research suggests PTSD or its subclinical forms are linked to a chronic or life-threatening medical problems and risky behaviors, many of which may require preventive intervention.

A study conducted by Harvard and Boston University researchers analyzed data from the Veterans Administration Normative Aging Study. Specifically, the researchers compared the health records of male veterans who had completed PTSD symptom questionnaires in 1986 and 1990. The men were followed for 10-15 years and their health status documented. A striking finding was the veterans with more PTSD symptoms were more likely to have heart attacks in subsequent years. The researchers noted that "For each level increase in symptoms on the 1990 assessment, the risk of heart attack or chest pain rose 18 percent - even after controlling for smoking, alcohol use and high blood pressure.". A limitation of the study was that most participants had subclinical levels of PTSD and did not meet full diagnostic criteria. We also don't know if the same results would be found for women. The researchers also didn't measure how frequently the men exercised, so we don't know whether those with more PTSD symptoms were more likely to avoid exercising and this might have accounted for the effect.

Why might PTSD or its symptoms be bad for the veteran's health? Well-designed research studies have found that veterans with PTSD are more likely to smoke cigarettes than those without PTSD. People who are chronically anxious or "on edge" often smoke to calm themselves down or as a nervous habit. Also both experiencing trauma and having PTSD symptoms have been linked to a higher incidence of chronic pain complaints, especially low back pain and headaches. Here the picture gets complicated because many veterans returning from Iraq and Afghanistan also have mild traumatic brain injury (TBI) and have experienced concussions and been injured.This raises a "chicken and egg" problem in that the pain could be due to PTSD, TBI, the combination of the two, or all three conditions could be due to the original injury.

In other research, veterans with PTSD have been shown to have more autoimmune diseases, such as arthritis and psoriasis, than those without. In autoimmune diseases, the immune system becomes overactive, mistaking parts of the person's own body for a foreign object and mounting an immune response resulting in chronic inflammation. In PTSD, the person becomes hypervigiilant to threat, chronically on edge, and more likely to perceive neutral events as dangerous. Being in a constant state of alertness might stress out the heart and make the immune system hyperactive. In other research conducted by the Army, of veterans returning from Iraq, those with PTSD reported worse health status and had more missed workdays in the first year than those without. This raises the spectre of increased financial costs of PTSD due to disability and lower productivity. It is not yet known if these effects continue long-term.

A new research study, summarized this weekend in Science Daily, suggests a possible mechanism for PTSD's link with having shorter life. In this recent study, conducted by researchers at the San Francisco VA Medical Center and the University of California, San Francisco. veterans from Iraq and Afghanistan who were diagnosed with PTSD had shorter telomeres than those without. The study defined telomeres as "DNA-protein complexes that cap the ends of chromosomes and protect them from damage and mutations." They stated that "Short telomere length is associated with an increased risk of cancer, cardiovascular disease, and autoimmune and neurodegenerative diseases, as well as early death." Other analyses indicated that those in the PTSD group with more childhood traumas, including neglect, physical abuse or sexual abuse, had the shortest telomeres. This suggests a possible additive effect of PTSD and childhood traumas in predicting telomere length and risk for early mortality. Unfortunately, the study could not address this question directly because those without PTSD had few childhood traumas.

These results allude to possible hidden financial and personal costs of the wars that the US has participated in. These costs include healthcare, pain and suffering and disability. While mental health aspects of PTSD are widely publicized, less attention has been paid to the longer-term physical health risks. Implications for treatment are that veterans with PTSD should be monitored closely by their doctors, educated about the possible health risks, and given preventive lifestyle and mind-body interventions as well as medications for PTSD. Integrative interventions such as yoga, tai chi, or meditation treat the whole person, may involve breathing stretching, or relaxation, and, if tolerated by the veterans, may be good adjuncts to psychiatric and/or Cognitive-Behavioral treatment for PTSD. Thinking about PTSD as just a mental health issue that can be medicated away does a disservice to our nation's veterans. Instead, seeing PTSD as a complex mind-body problem opens the door for thinking about innovative and integrative healthcare solutions.

Melanie Greenberg PhD is a Clinical Health Psychologist with a private practice in Marin County, CA. She specializes in helping individuals deal with life stress due to chronic illness, role demands, traumas and major life transitions. She is also available for workshops and speaking engagements. To find out more about my clinical practice, background, and scientific publications, visit my website athttp://www.melanieagreenbergphd.com. For more articles, check out my blog http://marinpsychologist.blogspot.com.

There are few experiences more terrifying than a panic attack. These extreme and sudden episodes of intense fear are often accompanied by physical symptoms such as chest pain, heart palpitations, shortness of breath, dizziness, or abdominal distress. And unless treated, recurring panic disorders can incapacitate an individual physically, mentally, and even socially.

While the exact causes of panic disorder are still the subject of intense scientific debate, the most widely accepted notion is that the periaqueductal gray area of the brain – or the PAG – is involved with the panic response, and that the neurotransmitter serotonin plays a key role in modulating this region.

In this podcast, we speak with Dr. Frederico Graeff of the University of Sao Paulo. Dr. Graeff is one of the leading experts in the scientific study of anxiety and panic. Be sure to join us as we talk about the key brain systems involved with both disorders, and what exactly differentiates panic at a neurobiological level.